Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postoperative chemoradiotherapy was introduced to improve the survival of patients with esophageal squamous cell carcinoma (ESCC). However, considerable number of patients still die of cancer recurrence despite curative operation plus chemoradiotherapy. This indicates that some ESCCs are chemoradio-resistant. To prevent unnecessary treatment and to improve the effect of post-operative adjuvant therapy, it seems to be important to investigate biological markers of chemoradio-sensitivity in ESCC. Loss of Bax expression has been reported to be associated with poor response to chemotherapy in breast cancer, and Bax promotes apoptosis in cells. Abnormal expression of Bax may play an important role in chemoradio-sensitivity in malignant tumors. In this study, we retrospectively investigated the prognostic significance of the expressions of Bax and p53 in patients with ESCC. Immunoreactivities of Bax and p53 were evaluated in 141 surgically resected ESCC by using monoclonal antibodies. Prognoses of 141 patients with or without postoperative chemoradiotherapy were compared among groups with high and low expressions of Bax or p53. High immunoreactivities of Bax and p53 were detected in 49 cases (33.1%) and in 70 cases (47.3%), respectively. Loss of Bax expression was detected more frequently in p53-positive tumors. Bax expression correlated with favorable prognosis (P=0.016) in 57 patients with postoperative chemoradiotherapy. However, in 84 patients without adjuvant therapy, the prognostic significance of Bax was minimal. Moreover, in patients with or without postoperative chemoradiotherapy, p53 expression did not correlate with the prognosis. Bax expression may be a good marker for chemoradio-sensitivity in patients with ESCC.
Int J Mol Med 2001 Apr
PMID:Bax expression as a prognostic marker of postoperative chemoradiotherapy for patients with esophageal cancer. 1125 84

Mammography is the primary imaging modality for screening of breast cancer and evaluation of breast lesions (T staging). Ultrasonography is an adjunctive tool for mammographically suspicious lesions, in patients with mastopathy and as guidance for reliable histological diagnosis with percutaneous biopsy. Dynamic enhanced magnetic resonance mammography (MRM) has a high sensitivity for the detection of breast cancer, but also a high false positive diagnosis rate. In the literature, MRM is reported to have a sensitivity of 86-96%, a specificity of 64-91%, an accuracy of 79-93%, a positive predictive value (PPV) of 77-92% and a negative predictive value (NPV) of 75-94%. In unclarified cases, metabolic imaging using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) can be performed. In the literature, FDG PET is reported to have a sensitivity of 64-96%, a specificity of 73-100%, an accuracy of 70-97%, a PPV of 81-100% and an NPV of 52-89%. Furthermore, PET or PET/CT using FDG has an important role in the assessment of N and M staging of breast cancer, the prediction of tumour response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy, and the differentiation of scar and cancer recurrence. Other functional radionuclide-based diagnostic tools, such as scintimammography with sestamibi, peptide scintigraphy or immunoscintigraphy, have a lower accuracy than FDG PET and, therefore, are appropriate only for exceptional indications.
Eur J Nucl Med Mol Imaging 2004 Jun
PMID:FDG PET and other imaging modalities in the primary diagnosis of suspicious breast lesions. 1513 34

Fluorescence in situ hybridization (FISH) testing is used to detect bladder cancer in urine specimens. The purpose of this study was to determine whether there are associations between the percentage of chromosomally abnormal cells by FISH and time to bladder cancer recurrence and progression to metastasis. Clinical records were searched to identify patients with urine FISH results, history of non-invasive bladder cancer, and at least one follow-up pathological diagnosis. Covariates analyzed included age, gender, smoking status, treatment after FISH, cystoscopy result, and prior stage of bladder cancer. The percentage of abnormal cells (hazard ratio [HR] 1.03, 95% CI 1.02-1.03; P < 0.001), age (HR 1.02, 95% CI 1.00-1.03; P = 0.033), male gender (HR 0.60, 95% CI 0.41-0.87; P < 0.001), treatment (HR 0.37, 95% CI 0.25-0.55; P < 0.001), and history of TIS/T1-stage tumors (HR 1.66, 95% CI 1.23-2.24; P = 0.001) were significantly associated with time to cancer recurrence. Time to invasive cancer was significantly associated with the percentage of abnormal cells (HR 1.02, 95% CI 1.01, 1.03; P < 0.001), history of TIS/T1 tumor (HR 3.73, 95% CI 1.88, 7.38; P = 0.001), and treatment (HR 0.33, 95% CI 0.13, 0.83; P = 0.019), suggesting that the percentage of abnormal cells independently predicts cancer recurrence and progression to invasive disease in patients with a history of non-invasive bladder cancer.
J Mol Diagn 2009 Mar
PMID:Quantitative fluorescence in situ hybridization and its ability to predict bladder cancer recurrence and progression to muscle-invasive bladder cancer. 1917 55

We describe a strategy for the analysis of experimentally derived gene expression signatures and their translation to human observational data. Sparse multivariate regression models are used to identify expression signature gene sets representing downstream biological pathway events following interventions in designed experiments. When translated into in vivo human observational data, analysis using sparse latent factor models can yield multiple quantitative factors characterizing expression patterns that are often more complex than in the controlled, in vitro setting. The estimation of common patterns in expression that reflect all aspects of covariation evident in vivo offers an enhanced, modular view of the complexity of biological associations of signature genes. This can identify substructure in the biological process under experimental investigation and improved biomarkers of clinical outcomes. We illustrate the approach in a detailed study from an oncogene intervention experiment where in vivo factor profiling of an in vitro signature generates biological insights related to underlying pathway activities and chromosomal structure, and leads to refinements of cancer recurrence risk stratification across several cancer studies.
Stat Appl Genet Mol Biol 2009
PMID:A bayesian analysis strategy for cross-study translation of gene expression biomarkers. 1922 78

Local recurrence is a therapeutic challenge for radiofrequency ablation (RFA) in treatment of small solid focal malignancies. Here we show that RFA induced heat shock proteins (HSPs) expression and high mobility group box-1 (HMGB1) translocation in xenografted melanoma, which might create a proinflammatory microenvironment that favors tumor antigen presentation and activation of the effector T cells. On this basis, we investigate whether a prime-boost strategy combining a prime with heat-shocked tumor cell lysate-pulsed dendritic cell (HT-DC) followed by an in situ boost with radiofrequency thermal ablation can prevent local tumor recurrence. The combination treatment with HT-DC and RFA showed potent antitumor effects, with >or=90% of tumor recurrence abrogated following RFA treatment. By contrast, prevaccination with unheated tumor lysate-pulsed DC had little effect on tumor relapse. Analysis of the underlying mechanism revealed that splenocytes from mice treated with HT-DC plus RFA contained significantly more tumor-specific, IFN-gamma-secreting T cells compared with control groups. Moreover, adoptive transfer of splenocytes from successfully treated tumor-free mice protected naive animals from tumor recurrence following RFA, and this was mediated mainly by CD8(+) T cells. Therefore, the optimal priming for the DC vaccination before RFA is important for boosting antigen-specific T cell responses and prevention of cancer recurrence.
Mol Ther 2009 Dec
PMID:Abrogation of local cancer recurrence after radiofrequency ablation by dendritic cell-based hyperthermic tumor vaccine. 1977 43

Recently, the detection of occult cancer cells in peripheral blood has received a great deal of attention regarding the prediction of postoperative cancer recurrence and for novel strategies of adjuvant therapy. The aim of this study was to establish a new molecular diagnostic method of detecting circulating tumor cells. Gastric cancer SGC-7901 cells in 2 ml blood from healthy volunteers were serially diluted. Additional peripheral blood samples were collected from 90 patients and 27 healthy volunteers. Real-time reverse transcription-polymerase chain reaction was used to detect the levels of microRNA-106a (miR-106a) and microRNA-17 (miR-17). Receiver operating characteristics (ROC) curves were constructed. In recovery experiments, a significant correlation between the number of cancer cells and the levels of both miR-106a (r = -0.906, p = 0.037) and miR-17 (r = -0.912, p = 0.031) was found. In preoperative and postoperative patient groups, miR-106a and miR-17 levels were significantly higher than those in controls. The areas under the ROC curve for miR-106a, miR-17, and combination were 0.684 (p = 0.0066), 0.743 (p = 0.0001), and 0.741 (p = 0.0002), respectively. Our results indicate that the detection of miRNA in peripheral blood may be a novel tool for monitoring circulating tumor cells in patients with gastric cancers.
J Mol Med (Berl) 2010 Jul
PMID:Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. 2034 19

Exciting new studies are increasingly strengthening the link between mitochondrial mutagenesis and tumor progression. Here we provide a comprehensive review and meta-analysis of studies reporting on mitochondrial DNA mutations in common human cancers. We discuss possible mechanisms by which mitochondrial DNA mutations may influence carcinogenesis, outline important caveats for interpreting the detected mutations--particularly differentiating causality from association--and suggest how new mutational assays may help resolve fundamental controversies in the field and delineate the origin and expansion of neoplastic cell lineages. Finally, we discuss the potential clinical utility of mtDNA mutations for improving the sensitivity of early cancer diagnosis, rapidly detecting cancer recurrence, and predicting the disease outcome.
Environ Mol Mutagen 2010 Jun
PMID:Generation, function, and prognostic utility of somatic mitochondrial DNA mutations in cancer. 2054 83

The comparative proteomic study of cell surfaces of native and drug-treated cancer cells was performed. To this end, cell proteomic footprinting, which reflects the mass spectrometry profiling of cell surface proteins, was applied to breast adenocarcinoma cells (MCF-7), which were untreated or treated with doxorubicin, tamoxifen, or etoposide. The footprints of drug-treated cells were compared with the footprints of untreated cells and the footprint of a randomly selected control cancer cell culture. It was found that drug-treated cells have reproducible, pronounced, and drug-specific changes in cell surface protein expression. Cytotoxicity assays, which are an in vitro model of human antitumor vaccination, revealed that the degree of these changes correlates directly with the ability of the cancer cells to escape cell death induced by a cytotoxic T-cell-mediated immune response. Moreover, cancer cells escape from the immune response was linearly approximated (R(2) equal to 0.99) with the degree by which their proteomic footprints diverged from the footprint of the targeted (native) cancer cells. From these findings, it was concluded that the design of anticancer vaccines intended to prevent cancer recurrence after primary treatment should consider the drug-specific changes in cancer cell-surface antigens. Such changes can be easily identified by cell proteomic footprinting, renewing hopes for development of efficient cellular cancer vaccines.
Mol Cell Proteomics 2012 Feb
PMID:Proteomic footprinting of drug-treated cancer cells as a measure of cellular vaccine efficacy for the prevention of cancer recurrence. 2207 4

Increasing evidence supports the existence of a subpopulation of cancer cells capable of self-renewal and differentiation into diverse cell lineages. These cancer stem-like or cancer-initiating cells (CICs) also demonstrate resistance to chemo- and radiotherapy and may function as a primary source of cancer recurrence. We report here on the isolation and in vitro propagation of multicellular ovarian cancer spheroids from a well-established ovarian cancer cell line (OVCAR-3). The spheroid-derived cells (SDCs) display self-renewal potential, the ability to produce differentiated progeny, and increased expression of genes previously associated with CICs. SDCs also demonstrate higher invasiveness, migration potential, and enhanced resistance to standard anticancer agents relative to parental OVCAR-3 cells. Furthermore, SDCs display up-regulation of genes associated with epithelial-to-mesenchymal transition (EMT), anticancer drug resistance and/or decreased susceptibility to apoptosis, as well as, down-regulation of genes typically associated with the epithelial cell phenotype and pro-apoptotic genes. Pathway and biological process enrichment analyses indicate significant differences between the SDCs and precursor OVCAR-3 cells in TGF-beta-dependent induction of EMT, regulation of lipid metabolism, NOTCH and Hedgehog signaling. Collectively, our results indicate that these SDCs will be a useful model for the study of ovarian CICs and for the development of novel CIC-targeted therapies.
Mol Cell Biochem 2012 Apr
PMID:Isolation and characterization of stem-like cells from a human ovarian cancer cell line. 2216 Sep 25

Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix components crucial for tumor growth, invasion and metastasis. MMPs are controlled by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). We and others have demonstrated that MMPs and TIMPs are especially important in the process of tumor invasion, progression and the metastasis of colorectal cancer (CRC). It has been proposed that MMPs and TIMPs might play a part not only in tumor invasion and initiation of metastasis but also in carcinogenesis from colorectal adenomas. Several recent studies demonstrated that high preoperative serum or plasma MMP-2, MMP-9 and TIMP-1 antigen levels are strong predictive factors for poor prognosis in patients with CRC and their determination might be useful for identification of patients with higher risk for cancer recurrence. MMP-9 and TIMP-1 have significant potential tumor marker impact in CRC. Their diagnostic sensitivity is consistently higher than those of conventional biomarkers. The pharmacological targeting of CRC by the development of a new generation of selective inhibitors of MMPs, that is highly specific for certain MMPs, is a promising and challenging area for the future.
Int J Mol Sci 2012 Oct 16
PMID:The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. 2320 50


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